What does a high ferritin level indicate and how is it treated?

Elevated Ferritin at 348.2 μg/L: Clinical Significance and Management

A ferritin level of 348.2 μg/L is mildly elevated and most commonly indicates an underlying inflammatory condition, metabolic syndrome, liver disease, or alcohol consumption rather than true iron overload—the priority is identifying and treating the underlying cause, not the ferritin level itself. 1, 2

Initial Diagnostic Evaluation

Your first step is to measure transferrin saturation (TS) alongside the ferritin to properly evaluate iron status, as ferritin alone is insufficient for diagnosis. 1

Interpret Based on Transferrin Saturation

• If TS ≥ 45%: Proceed to HFE genotype testing to evaluate for hereditary hemochromatosis 1
• If TS < 45% (most likely scenario at this ferritin level): Investigate non-iron overload causes 1

Most Likely Causes at This Ferritin Level

At 348.2 μg/L, 90% of cases are due to non-iron overload conditions where phlebotomy is not appropriate. 3 The most common etiologies include:

Primary Considerations

• Metabolic syndrome and fatty liver disease: Check liver enzymes (ALT, AST), assess for obesity, diabetes, and hepatic steatosis 1, 2, 4
• Alcohol consumption: Even moderate intake elevates ferritin; quantify alcohol use 1, 3
• Chronic inflammatory conditions: Measure CRP and ESR to detect systemic inflammation 1
• Liver disease: Viral hepatitis, NAFLD, and other hepatopathies commonly elevate ferritin 4
• Malignancy: The most frequent cause in large case series of elevated ferritin 5
• Infection: Active or recent infections raise ferritin as an acute-phase reactant 5, 6

Less Common but Important

• Chronic kidney disease: Particularly if anemic, as ferritin interpretation differs in this population 7
• Autoimmune hepatitis: Elevated ferritin >2.1-fold upper limit of normal at diagnosis has been associated with subsequent biochemical remission 7

Management Strategy

Treat the underlying condition, not the ferritin number. 1

For Metabolic/Lifestyle Causes

• Weight loss through dietary modification and increased physical activity for metabolic syndrome 2
• Reduce alcohol intake if excessive consumption identified 2
• Address diabetes and fatty liver disease with standard therapies 2

When to Refer to Specialist

Referral to gastroenterology, hematology, or iron overload specialist is appropriate if: 3

• Ferritin >1000 μg/L (not applicable in your case)
• Cause remains unclear after initial evaluation
• Evidence of organ damage present

Critical Thresholds to Remember

Your ferritin of 348.2 μg/L is well below concerning thresholds:

• <500 μg/L: Generally safe range; no concern for iron toxicity 7
• 500-1000 μg/L: Warrants closer evaluation but rarely indicates iron overload alone 7
• >1000 μg/L: Critical threshold requiring liver disease assessment and possible biopsy if accompanied by elevated liver enzymes 1, 8
• >10,000 μg/L: Suggests life-threatening conditions (hemophagocytic lymphohistiocytosis, adult-onset Still's disease, macrophage activation syndrome) requiring urgent specialist referral 1, 5, 9

Common Pitfalls to Avoid

• Do not use ferritin alone to diagnose iron overload without checking transferrin saturation 1
• Do not initiate phlebotomy based solely on mildly elevated ferritin—this is only appropriate for confirmed hemochromatosis with TS ≥45% 1, 2
• Do not supplement iron in patients with elevated ferritin 1
• Remember ferritin is an acute-phase reactant: Levels increase with any inflammation, making interpretation context-dependent 6

Specific Next Steps for Your Patient

1. Order serum iron, total iron binding capacity, and calculate transferrin saturation 1, 2
2. Check liver function tests (ALT, AST, GGT) 1
3. Measure inflammatory markers (CRP, ESR) 1
4. Assess for metabolic syndrome components: BMI, glucose, lipid panel 2
5. Quantify alcohol consumption 3
6. If TS ≥45%, proceed to HFE genetic testing 1